Additionally, is also used in tissue engineering. Tissue

Additionally, viruses have also been developed for carrying hereditary material into mammalian cells as efficient vectors.

There are various examples of RGD-modified viruses which utilizes for gene delivery are shown in Table 5. Table 5. RGD-modified viruses for gene delivery. Gene Production Tumor model hybrid GFP or Luc reporter genes RGD4C/AAV/phage Human M21 Melanoma Human U87 glioblastoma (Przystal et al., 2013) shRNA Ad/CD-PEG500-RGD Various cancer cells (Kim et al., 2011) Firefly luciferase gene (Adenovirus) Ad-RGD Mouse TS cells (Katayama et al., 2011)  4.

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3.4. Bioengineering Application: RGD For Tissue Engineering  Now a day, the RGD peptide is also used in tissue engineering. Tissue engineering is the application of biology and engineering principles, in which biological alternatives are prepared and used to repair, preserve or to advance the function of biological tissues.

The implanted or substituted substrates should give structural support for damaged tissues, interact with these tissues and facilitate rejuvenation of the damaged area are some of the basic requirements in tissue engineering. RGD peptides are able to increase the interaction between various types of cell with the different types of biomaterials (Bellis, 2011).In this branch first the required RGD molecule is identified then modified (functionalized) after processing and sterilization. Then biomaterials which are used for tissue engineering are modified with previously functionalized RGD peptides. Now RGD peptide modified biomaterial is ready for use.

The attached RGD enhances cell adhesion of biomaterials via the integrin receptors, and therefore, helps in the processing of tissue engineering. Cell adhesion to biomaterials can be controlled by integrins through different mechanisms like adsorbing, engineering and depositing as shown below with figure 4.(a) Adsorbing: adhesive extracellular ligands (RGD) on biomaterial surfaces are adsorbed on cells with the integrins induction; (b) Engineering: RGD motifs are engineered to biomaterials at the interface site; (c) Depositing: thus cells deposit more bioadhesive ligands (Figure 4) (Garcia, 2005). Figure 4. Mechanisms controlling cell adhesion to biomaterials Other RGD-modified biomaterials with experimental models are listed in Table 6.Table 6. RGD-peptide modified biomaterials.

Class Biomaterials Compound Tumor model Polymer   PCL (polycaprolactone) PCL RGD-modified 3D-PCL Bone marrow stromal cells (Zhang et al., 2009) PCL RGD-PCL Vascular grafts rabbit carotid artery (Zheng et al., 2012) Poly (ethylene imine)- poly(2-vinyl-4,4- dimethylazlactone) RGD-PEI/PVDMA Human corneal  epithelial (Tocce et al., 2013) Alginate scaffolds   RGD-immobilized  alginate scaffolds Cardiac cell (Shachar et al., 2011) Inorganic Materials Ti6-Al-4V pins   RGD-coated Ti6-Al-4V pins Rabbit femurs (Chen et al., 2011) Hydroxyapatite (HA) RGD-coated HA Rat tibiae (Hennessy et al., 2008) Proteins   Nephronectin RGD nephronectin Cardiomyocytes (Patra et al.

, 2012) Spider silk RGD-modified spider silk BALB/3T3 mouse fibroblasts (Wohlrab et al., 2012)  The RGD peptides also functioned as extracellular adhesive protein which may help bone regeneration and play a significant role in the osseointegration process of osteoblasts. RGD peptides immobilized on titanium (Ti) metal surfaces and then interacting with integrins, increased early osteoblastic cell attachment and successive differentiation hence improving bone healing (Chen et al., 2011). RGD peptides are also useful for the regeneration of damaged cornea. Cornea is the important part of our eyes. So many factors like age, diseases may be responsible for damaged corneas (Jo et al.

, 2011). Nowadays, the science of tissue engineering have the possibility to repair the damaged corneas. Gil et al., 2010, had showed that the silk human cornea structure could be modified with RGD peptide which helps in the interaction of corneal stroma tissue with proteoglycan-rich extracellular matrix (Gil et al., 2010). Corneal stromal tissue may become a constructive technique for engineering human cornea due to replication of the structure and architecture of actual human cornea.

Thereafter, this technique can also be helpful for repairing of other tissue systems of the eyes.  RGD peptides are helpful in the vascular grafting in various cardiovascular diseases. Most of the cardiovascular diseases are caused by the platelet adhesion or obstruction of other molecules in the heart capillaries.

Therefore, these conditions increase the demand of vascular grafting for the treatment of diseases, so it is important to build up effective grafting system with bio-functionalities. Wang et al., 2011 have discovered a novel surface RGD-coating method on hydrophobic polymer like PCL by using naphthalene modified RGD peptide (Nap-FFGRGD). The RGD coating on the surface of polymer reduces hydrophobicity; thus showed higher cell adhesion and spreading (Wang et al., 2011).

This characteristic of RGD may help in the vascular graft and many cardiovascular diseases.  Inhibition of platelet adhesion may be enhanced with the help of RGD-modified grafts, which may enhance endothelium formation, cell infiltration, and regeneration of smooth muscle and hence show less obstruction in capillaries. The developed PCL-RGD based graft system may be a capable candidate for the small-diameter vascular grafts for cardiovascular disease (Zhang et al.

, 2009).